Recovery can and frequently does occur after traumatic brain injury (TBI). However, this recovery is often incomplete, resulting in profound lifelong impairments in function. Little is known about the neural mechanisms that contribute to recovery after brain injury, but recent studies suggest that neurogenesis may be important. The objective of this proposal is to use a rodent model of TBI, the fluid percussion brain injury model (FP), to determine if acute increases in neural progenitor cells in the hippocampus provide a neural substrate for recovery of cognitive function. Specific Aim 1 determines if there is an association between cognitive recovery and neural progenitor cells in the hippocampus following FP injury. FP injury causes persistent cognitive deficits in mature animals, which are attenuated by environmental enrichment. Are these improvements in cognition attributable to neural progenitors? If yes, then there should be a temporal correspondence between the time required for progenitors to mature and the onset of improvements in behavior. To test this, we will compare time-dependent changes in cognitive function and the fate of the neural progenitors (numbers, phenotype, and migration) within the hippocampus following FP injury in animals with and without enrichment, and in sham injured controls. Specific Aim 2 determines if blocking injury-induced increases in neurogenesis attenuates environmental improvements in cognitive function after FP injury. We will use low dose brain irradiation to selectively target neural stem cells in animals subjected to a FP injury with and without enrichment, and in sham injured controls sham. Cognition and the fate of neural progenitors will be compared across groups. Specific Aim 3 determines if transient injury-induced increases in neural progenitors create a "critical period" for interventions that enhance recovery of function after FP injury. We will investigate this by subjecting animals to a FP injury, followed by either early or delayed environmental enrichment. Together, the proposed studies will help determine whether endogenous neural progenitor cells can contribute to recovery after brain injury. This information will contribute to our understanding of neural substrates associated with brain repair, and ultimately, to interventions that will enhance functional recovery.